We evaluated the efficacy and safety of 24 cycles of Dara in combination with carfilzomib (K), lenalidomide (R), and dexamethasone (d) without autologous stem cell transplant (ASCT) in newly diagnosed multiple myeloma (NDMM) irrespective of ASCT eligibility in a single-arm, phase II study. The primary endpoint was the rate of stringent complete response (sCR) and/or measurable residual disease (MRD) < 10−5 by next-generation sequencing (NGS) at the end of cycle 8 (C8). MRD was also assessed on peripheral blood samples using both the EXENT® system and liquid chromatography–mass spectrometry (LC–MS). Forty-two patients entered the treatment phase; forty were evaluable for the primary endpoint. The rate of sCR and/or MRD < 10−5 following C8 was 30/40 (75%), meeting the statistical threshold for efficacy. The 10−6 MRD negative rate improved with treatment beyond C8. Agreement between EXENT® and NGS was high and increased over time; agreement between LC-MS and NGS was lower. The estimated 3-year progression-free survival progression-free survival was 85%, and 3-year overall survival was 95%. Upper respiratory infections occurred in 67% (7% grade 3–4). There were no treatment-related deaths. Extended frontline Dara-KRd induced a high rate of sCR and/or MRD negativity; the rate and depth of MRD negativity improved beyond C8.
我们在一项单臂II期研究中评估了达雷妥尤单抗联合卡非佐米、来那度胺和地塞米松（Dara-KRd）24周期方案在新诊断多发性骨髓瘤（NDMM）患者中的疗效与安全性，这些患者无论是否符合自体干细胞移植（ASCT）条件均未接受ASCT。主要研究终点为第8周期（C8）结束时通过二代测序（NGS）检测的严格意义的完全缓解（sCR）率和/或可测量残留病（MRD）＜10−5的比例。同时采用EXENT®系统与液相色谱-质谱联用技术（LC-MS）对外周血样本进行MRD评估。42例患者进入治疗阶段，其中40例可用于主要终点评估。C8后sCR和/或MRD＜10−5的比例为30/40（75%），达到预设的疗效统计学阈值。10−6水平MRD阴性率在C8治疗后持续改善。EXENT®与NGS检测结果一致性较高且随时间推移持续提升；LC-MS与NGS的一致性相对较低。预估3年无进展生存率为85%，3年总生存率为95%。67%患者发生上呼吸道感染（其中3-4级占7%），无治疗相关死亡事件。延长前线Dara-KRd治疗可诱导较高比例的sCR和/或MRD阴性，且MRD阴性率与深度在C8治疗后持续提升。
肿瘤(癌症)患者之家